Low Serum Magnesium Levels Are Associated With Hemorrhagic Transformation After Thrombolysis in Acute Ischemic Stroke

So what the fuck is the solution?

1. Test for magnesium deficiency?

2. How would you bring low levels up fast enough to not slow down thrombolysis intervention?

Low Serum Magnesium Levels Are Associated With Hemorrhagic Transformation After Thrombolysis in Acute Ischemic Stroke

Zicheng Cheng¹, Xiaoyan Huang¹, Farah Mohamed Muse¹, Lingfan Xia¹, Zhenxiang Zhan¹, Xianda Lin², Yungang Cao¹ and Zhao Han^1*

• ¹Department of Neurology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
• ²Department of Neurology, The Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou, China

Background: In patients with acute ischemic stroke, hemorrhagic transformation is a major complication after intravenous thrombolysis. This study aimed to investigate the relationship between serum magnesium levels and hemorrhagic transformation (HT) after thrombolytic therapy.

Methods: We retrospectively analyzed data from 242 patients who received thrombolytic therapy at the Second Affiliated Hospital of the Wenzhou Medical University in China. Baseline serum magnesium levels were measured before intravenous thrombolysis, and the occurrence of HT was evaluated using computed tomography images reviewed within 24–36 h after therapy. The relationship between serum magnesium levels and HT was examined using multivariate logistic regression, subgroup analysis, and restricted cubic spline models.

Results: Of the 242 included patients, 43 (17.8%) developed HT. Patients with HT had significant lower serum magnesium levels than those without HT (0.81 ± 0.08 vs. 0.85 ± 0.08 mmol/L, p = 0.007). Multivariable logistic regression analysis indicated that patients with higher serum magnesium levels had lower risk of HT (OR per 0.1-mmol/L increase 0.43, 95% CI 0.27–0.73, p = 0.002). However, this association did not persist when baseline levels of serum magnesium were higher than the median value (0.85 mmol/L) in subgroup analysis (OR per 0.1-mmol/L increase 0.58, 95% CI 0.14–2.51, p = 0.47). This threshold effect was also observed in the restricted cubic spline model when serum magnesium levels were above 0.88 mmol/L. No association between symptomatic HT and serum magnesium levels was observed in our study (OR per 0.1-mmol/L increase 0.52, 95% CI 0.25–1.11, p = 0.092).

Conclusions: Lower serum magnesium levels in patients with ischemic stroke are associated with an increased risk of HT after intravenous thrombolysis, but perhaps only when serum magnesium is below a certain minimal concentration.

Introduction

Intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) is the preferred treatment for acute ischemic stroke patients in super earlier period (≤ 4.5 h) (1). However, hemorrhagic transformation (HT) is common in patients with IVT, occurring as a consequence of coagulation dysfunction and blood-brain barrier (BBB) disruption induced by rt-PA (2, 3). Limited administration of thrombolytic drugs in stroke patients is largely due to the fear of HT. Since patients with HT are susceptible to early death or long-term disability (4, 5), it is imperative to identify the modifiable risk factors of HT after IVT.

Magnesium is an abundant endogenous neuroprotective agent that has close association with ischemic stroke (6). It also maintains the integrity of the vascular endothelial barrier through anti-inflammatory and anti-oxidation effects (7). Brain microvascular endothelium is the fundamental component of BBB and the initiation of ischemia-related BBB disruption is predominantly triggered by endothelial damage (8). Recent evidence indicates the protective effect of magnesium on BBB in rats with transient focal cerebral ischemia (9). In addition, magnesium is involved in the coagulation cascade (10, 11) and platelet activation (12); magnesium deficiency would lead to dysfunction of coagulation system. The relationship between serum magnesium levels and functional outcomes in patients with acute ischemic stroke has been widely studied. But two large-sample randomized controlled trials [the IMAGES (Intravenous Magnesium Efficacy in Stroke) trial and the FAST-MAG (Field Administration of Stroke Therapy–Magnesium) trial] showed regrettable results, which early intravenous magnesium sulfate therapy did not improve the outcomes for patients with acute stroke (13, 14). By contrast, there are very few studies on the association between serum magnesium levels and the occurrence of HT. These studies had inconsistent conclusions and did not specifically address patients with IVT (15, 16). Thus, we investigated the association of serum magnesium levels with development of HT in patients with acute ischemic stroke after IVT.